Glycosylation quality control by the Golgi structure

Glycosylation is a ubiquitous and essential modification that occurs on proteins and lipids in all living cells. Asparagine‐linked protein N‐glycosylation, the most complex glycosylation, initiates in the endoplasmic reticulum (ER) and matures in the Golgi apparatus. This process not only requires an accurate distribution of processing machineries, such as glycosyltransferases, glycosidases and nucleotide sugar transporters, but also needs an efficient, and well‐organized factory that is responsible for the fidelity and quality control of sugar chain processing. In addition, accurate glycosylation must occur in coordination with protein trafficking and sorting. These activities are carried out by the Golgi apparatus, a membrane organelle in the center of the secretory pathway. To accomplish these tasks, the Golgi has developed into a unique stacked structure of closely aligned flattened cisternae in which Golgi enzymes reside. We have developed a multidisciplinary approach to dissect the molecular mechanism of Golgi structure formation and its significance in protein glycosylation [1]. We found that Golgi cisternal stacking is required for accurate glycosylation in interphase cells [2,3]. We also found that in mitosis, key Golgi enzymes are inactivated This work has significant impact in understanding human diseases in which the Golgi becomes abnormal. For example, in Alzheimer's disease the Golgi is abnormally fragmented, which accelerate amyloidocleavage of the amyloid beta (Aβ) precursor protein APP. Significantly, rescue of the Golgi structure reduces Aβ production [4]. Our study suggests the Golgi as a potential drug target for disease treatment. In addition, we have made surprising discoveries that some Golgi proteins are O‐GlcNAcylated and some Golgi glycosylation enzymes are regulated by phosphorylation during the cell cycle. Support or Funding Information NIH R01s NIH GM087364 and GM112786.